The present invention relates to a microneedle, to a microneedle array and to a method for the production thereof.
Microneedles are a promising alternative and addition to standard injection needles. Microneedles have dimensions which are in the order of magnitude of several tens to several hundreds of micrometers. Details of the microneedle, such as the tip, have dimensions, for example, of several micrometers to one or more nanometers. As a result of their relatively small dimensions, microneedles are intended to penetrate the skin essentially painlessly and without visibly damaging the skin. The needles are preferably as sharp as possible in order to minimize the feeling of being injected by keeping the force required to push the needle into the skin as small as possible, as a result of which the skin deforms as little as possible upon injection. By selecting the length of the microneedles, medicinal products and the like can be introduced at a predetermined depth below the surface of the skin.
Microneedles can be produced using production techniques which are known for the processing of semiconductors. As described in the article “Penetration-Enhanced Ultrasharp Microneedles and Prediction on Skin Interaction for Efficient Transdermal Drug Delivery” by N. Roxhed et al., Journal of Microelectromechanical Systems, vol. 16, no. 6, December 2007, microneedles are divided into two classes, based on the production techniques used. The first class is formed by needles which extend at right angles from the plane of the substrate (out-of-plane needles). The second class is formed by needles which extend approximately parallel to the plane of the substrate (in-plane needles). Since the needles are small, a number of microneedles are preferably used simultaneously for the injection of medicinal products. However, in practice it has proven difficult to produce two-dimensional arrays of in-plane needles.
Microneedles are divided further into hollow and solid microneedles. Solid microneedles can be used, for example, to introduce a medicinal product which has been applied to the surface of the needles beforehand as a coating layer. Hollow microneedles are provided with a passage or channel, so that the medicinal products can be introduced into or under the skin through the channel of the needle.
U.S. Pat. No. 6,533,949 B1 provides a method for producing hollow out-of-plane microneedles on a silicon substrate. The needles are formed by etching an approximately V-shaped slot into the surface of the substrate. Inside the V shape a hole is also etched. The V shape may be rounded. The hole and the slot are then passivated by providing them with a protective layer. After the protective layer has been applied, the surface of the substrate is etched by means of a selective anisotropical etching process. During this process, the silicon is selectively removed from the surface of the substrate, with a protuberance remaining along a <111> crystal plane remaining inside the slot. Following subsequent removal of the protective layers, the protuberances provided with the apertures therein form microneedles.
However, due to the etching process used, the circumference of the needles formed in accordance with the process of U.S. Pat. No. 6,533,949 B1 is uneven, as a result of which the skin is damaged when the microneedles are pushed into the skin. The unevenness of the circumference can be seen, for example, in FIG. 4 of the article “Silicon Micromachined Hollow Microneedles for Transdermal Liquid Transport”, Journal of Microelectromechanical Systems, vol. 12, no. 6, December 2003. In addition, the length and sharpness of the microneedles is limited by the production process. As a result of the limited length and/or sharpness of the needles, not all needles of an array penetrate the skin, which may result in leaks, that is to say that when liquid is used, this leaks away via the needles which have not penetrated the skin.
U.S. Pat. No. 5,928,207 provides an in-plane microneedle, comprising an elongate shaft which ends in a tip. The walls of the shaft are etched isotropically or anisotropically, while the tip has been etched isotropically. As a result of isotropical etching, the tip has a sharp end which is much flatter and narrower than the shaft. At the top side of the needle, the transition from the tip to the shaft is relatively abrupt, however, as a result of which said transition damages the skin when the needle penetrates it.
In addition to the above, all hitherto known microneedles in practice appear to have a sharpness which is at most comparable to the sharpness of a standard 30G injection needle, as supplied by Popper & Sons, Inc., N.Y. (USA). However, the sharpness of a 30G injection needle is not sufficient to prevent damage to the skin. In use, (a part of) the microneedle is pushed into the skin with a certain force, resulting in a ‘needle trauma’ and the injection can be felt. The skin is damaged, red and/or sensitive after the injection. In addition, the sharpness is insufficient for use on relatively soft skin, such as the skin on the underarm or the face of a human being.